Azaserine induces hepatocarcinoma in rats fed diets deficient in methyl supply (methionine or choline or both) but not, or only rarely, normal rats. The dietary effect appears to be exerted at initiation. Liver fractions from deficient rats activate azaserine in vitro to one or more compounds that induce lambda prophage in E. coli or a forward mutation in S. typhimurium more effectively than fractions from normal rats, a result that correlates with the dietary effect on hepatocarcinogenesis. We propose studies to: 1) confirm the dietary effect and its timing by feeding purified diets that differ only in methionine and choline; 2) use the in vitro system to identify and quantitate azaserine-DNA adducts formed after activation of azaserine by fractions from deficient or normal livers; 3) use in vitro and in vivo systems to identify and measure any persistent hepatic adducts in deficient and normal rats. azaserine induces pancreatic tumors in normal rats; rats are partially protected by high casein diets. We propose studies to: 1) investigate whether protection may be afforded by methionine or choline and, 2) using methods developed in the studies of liver, identify pancreatic DNA-azaserine adducts. The research proposed will provide information on interactions between diet and intiation of carcinogenesis in pancreas and liver that: 1) may be useful in designing diets to decrease carcinogenesis and 2) will contribute to understanding of carcinogenesis.